Locking sensor cartridge with integral fluid ports, electrical connections, and pump tube

ABSTRACT

A blood analyzer sensor cartridge comprises a housing having chamber and a sensor assembly within the chamber, a first fluid port having an articulated inlet aspiration tube for direct introduction of a sample, a first fluid path in the housing communicating the first fluid port with the sensor assembly, a second fluid port in the housing adapted for connection to an analyzer, and a second fluid path in the housing communicating the sensor assembly with the second fluid port, the articulated tube is pivotally mounted to the housing for selective orientation within a range of up to ninety degrees, the tube is moveable from a protective recess in the housing to a position normal to a face of the housing.

REFERENCE TO RELATED APPLICATIONS

This is a Continuation-in-part of PCT application Ser. No.PCT/US/97/0773 filed on May 6, 1997, and application Ser. No. 08/648,692filed on May 16,1996, now U.S. Pat. No. 5,718,816.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to systems for analyzing fluids, and moreparticularly to an system for mechanical, electrical, and fluidinterconnection of sensors to a blood analyzer.

2. Description of Related Art

In a variety of instances it is desirable to measure the partialpressure of blood gasses in a whole blood sample, concentrations ofelectrolytes in the blood sample, and the hematocrit value of the bloodsample. For example, measuring pCO₂, pO₂, pH, Na⁺, K⁺, Ca²⁺ andhematocrit value are primary clinical indications in assessing thecondition of a medical patient. A number of different devices currentlyexist for making such measurements. Such devices are preferably veryaccurate in order to provide the most meaningful diagnostic information.In addition, in an attempt to perform these analyses in close proximityto the patent, the devices which are employed to analyze a blood sampleare preferably relatively small. Furthermore, it is important to reducethe size of the cavities and pathways through which the analyte mustflow in order to reduce the amount of analyte required. For example,performing blood analysis using a small blood sample is important when arelatively large number of samples must be taken in a relatively shortamount of time. More particularly, patients in intensive care require asampling frequency of 15-20 per day for blood gas and clinical chemistrymeasurements, leading to a potentially large loss of blood duringpatient assessment. Furthermore, the amount of blood available may belimited, such as in the case of samples taken from a neonate. Inaddition, by reducing the size of the analyzer sufficiently to make theunit portable, analysis can be performed at the point of care. Also,reduced size typically means reduced turnaround time. Furthermore, inorder to limit the number of tests which must be performed it isdesirable to gather as much information as possible upon completion ofeach test.

In one blood analyzer currently in use, a sensor/calibrant packagecomprises a sensor assembly mounted within a housing. Thesensor/calibrant package also comprises a plurality of fluid pouchesmounted within the housing. These pouches hold calibrants and flushfluids necessary for the operation of the blood analyzer. A series oftubes and valves within the housing interconnect the sensors within thesensor assembly to each of the fluid pouches. Since the tubes whichtransport a sample to the sensor assembly are within the housing, theoperator of the blood analyzer can not see the sample as it flows intoand out from the sensor assembly. Accordingly, the operator cannotdetermine visually whether the sample has entered the sensor assembly.This can be a significant problem, since the operator may not visuallysee that a blockage has occurred in the fluid flow path.

A heater assembly is mounted to the housing in order to raise thetemperature of the fluids, the sensor assembly, and the sample to bemeasured. Raising the temperature allows the analysis of the sample tobe carried out at a predetermined temperature. Due to the thermal massof the components and fluids that must be heated, such blood analyzersmay not be used for one or more hours after a new sensor/calibrantpackage has been installed. Furthermore, the need for such a heatersubstantially increases the cost of the sensor/calibrant package.

In addition to requiring that the sensor/calibrant package be heated, itis necessary to hydrate the sensors within the sensor assembly. Suchhydration of the sensors takes one or more hours. Accordingly, the bloodanalyzer is not operational for one or more hours after installation ofa new sensor assembly. In many cases analysis must be performed atregular and closely spaced intervals. Accordingly, if the heating andtemperature stabilization time and the hydration time are relativelylong, the number of times such analysis can be performed within aparticular amount of time (i.e., turn around time) can be limited to anumber less than would otherwise be desirable.

The fluid interface between the fluid pouches and the sensor assemblymust be controlled to prevent fluid from pouches from flowing to thesensor assembly prior to installation of the sensor/calibrant package beinstalled in the blood analyzer. This requirement adds a measure ofcomplexity to the mechanical design of the sensor/calibrant package,thus increasing the cost for fabricating the sensor/calibrant package.Furthermore, the complex interface between the sensor/calibrant packageand the blood analyzer makes installation of the sensor/calibrantpackage more difficult, increases the chance that fluid will leak fromthe sensor, and can potentially increase the length of the fluid path(thus increasing the chance that a clot will occur and increasing therequired volume of the sample). A portion of elastomeric tubing whichinterfaces the sensor assembly to the fluid pouches and a refuse pouch(into which exhausted samples and other fluids are pumped) is stretchedover a concave surface. When the sensor/calibrant package is placedwithin the blood analyzer, a pump arm strokes the tubes in order tocreate a peristaltic pump, thus increasing the complexity of themechanical interface between the sensor/calibrant package and the bloodanalyzer. Further complicating the mechanical interface is the need toprovide a mechanism by which the blood analyzer can control the valveswithin the sensor/calibrant package. A first valve must be rotated toallow a controller within the blood analyzer to configure the fluidpath. A set of additional slide valves must be actuated uponinstallation of the assembly into the blood analyzer in order to openthe flow path from each of the fluid pouches.

The sensor assembly has a plurality of sensors formed on a front side ofa polymeric substrate along a flow path between an inlet and outletport. The fluid flow path is formed as a groove in a polymericsubstrate. Electrodes are formed in the substrate. The electrodescommunicate with a measurement flow channel formed in the substrate. Theelectrodes also communicate with a measurement flow channel which isformed by the combination of substrate and a cover plate.

The electrical interface between the sensor assembly and electronicsexternal to the sensor assembly is provided through an plurality ofcontacts fabricated on the rear surface of the substrate. These contactsslide against a spring loaded mating contact in the blood analyzer. Asthe contacts of the sensor assembly slide against the mating contactswithin the blood analyzer, the contacts of the sensor assembly andanalyzer are worn down. Therefore, after inserting and removing thecartridge from the blood analyzer a number of times, the electricalconnection between the external circuits within the blood analyzer andthe sensors within the sensor assembly will be degraded.

Due to the use of electrical slide contacts, the structure of theinterface between the elastomeric tubes and the pump, and theconfiguration of the valve controls, the sensor/calibrant package mustfirst be inserted into the blood analyzer, and then slide generally at aright angle to the insertion angle. This process makes installation ofthe sensor/calibrant package awkward and increases the risk that eitherthe electrical, mechanical, or fluid interface between thesensor/calibrant package and the blood analyzer will be faulty.

Furthermore, since the sensor is an integral part of thesensor/calibrant package, when a sensor fails (i.e., can no longerperform in accordance with specified parameters) the entiresensor/calibrant package must be replaced.

Accordingly, in as much as installation and fabrication of sensorswithin a blood analyzer are both cumbersome and susceptible to leaks,and long delays result after installation, it would be desirable toprovide an assembly which allows the operator of a blood analyzer toreplace merely the sensor assembly with a fast turn around time, nospecial training, and with highly reliable electrical, mechanical andfluid interface.

The aforementioned parent application solved many of the aboveenumerated problems of the prior art. However, a number of furtherimprovements are desirable. For example, in the aforementioned system,the sample is introduced into the system through a port in the analyzerand passes through plumbing therein to the sensor cartridge. This has anumber of disadvantages such as a longer fluid passage requiring alarger sample. The greater distance of travel of the sample alsointroduces a greater chance for contamination from gases and othermaterials.

Another problem is that the fluid passage in the analyzer becomescontaminated, not just from the blood but from calibrant materials whichhave salts in them.

Furthermore, it would be desirable to provide such an assembly whichfurther allows the user to see a blood sample as it enters, flowsthrough, and exits the sensor assembly.

SUMMARY OF THE INVENTION

The present invention is a sensor cartridge into which sensors areinstalled. The sensor cartridge allows the sensors to be easily andreliably installed into a blood analyzer. The cartridge includes sixbasic components: (1) a housing; (2) a housing cover; (3) a sensorassembly; (4) a “pump tube” assembly; (5) a right angle fluid coupling;and (6) a capture/release arm.

In accordance with the preferred embodiment present invention, thesensor assembly has an electrical connector mounted on the rear side ofthe assembly. The body of the connector protrudes through a firstopening in the housing. The walls of the first opening conform generallyto the profile of the protruding body of the connector. Thus, themechanical interface between the body of the connector and the walls ofthe first opening in the housing retain the sensor assembly in apredetermined position within the housing.

A plurality of inner walls within the housing locate the pump tubeassembly and the right angle fluid coupling within the housing. One endof the pump tube assembly is formed as a straight end fluid coupling andis coupled to the sensor assembly. The other end of the pump tubeassembly is formed as a right angle end fluid coupling. A portion of theright angle end fluid coupling protrudes through a second opening in thehousing. The walls which define the second opening conform to thatportion of the right angle end fluid coupling which protrudes throughthe housing. The right angle fluid coupling is essentially similar tothe right angle end fluid coupling of the pump tube assembly. A portionof the right angle fluid coupling protrudes through a third opening inthe housing in a manner similar to the protrusion of the right angle endfluid coupling of the pump tube assembly. Another portion of the rightangle fluid coupling is coupled directly to the sensor assembly.

In accordance with one embodiment of the present invention, a fourthopening in the housing receives a first boss which extends from theblood analyzer. The first boss is generally cylindrical and solid with a“ring-like” groove machined near the distal end of the boss.Alternatively, the boss may be formed as an elongated structure having arectangular, oval, or other cross-section. In accordance with thisembodiment, a second boss is formed in the housing as a hollowedcylinder having an inner diameter which is nearly equal, but slightlylarger than the outer diameter of the first boss. The outer diameter ofthe second boss is greater than the inner diameter by an amount which isessentially equal to the thickness of the housing walls.

The capture/release arm has an opening through which the first bossprotrudes. The arm is resiliently held in place such that an inner edgeof the opening is captured within the ring-like groove in the boss thatextends from the blood analyzer when the cartridge is installed in theblood analyzer. A portion of the arm extends beyond the housing to allowan operator to press the arm and thus release the edge of the arm fromthe groove in the boss.

Electrical contacts of the connector on the rear side of the sensorassembly are aligned to mating electrical contacts of the blood analyzeras the sensor assembly is being installed by alignment of the boss whichextends from the blood analyzer to mate with the boss which extends fromthe housing, and alignment of two male fluid connectors, one of whichmates with the right angle fluid coupling and the other of which mateswith the right angle end fluid coupling of the pump tube assembly. Eachof these will engage with the mating member prior to the electricalcontacts of the sensor assembly engaging the electrical contacts of theblood analyzer. Accordingly, the electrical contacts of the sensorassembly will be in close alignment with the electrical contacts of theblood analyzer as the contacts approach one another.

A resilient portion of the pump tube assembly exits the housing at oneend and re-enters the housing at the same end, forming a “U” shapedloop. The loop formed by the pump tube is sufficiently flexible andresilient to allow the loop to be stretched over and into engagementwith a roller pump located on the blood analyzer. The roller pumprotates to massage the loop of the pump tube with which the roller pumpis engaged in order to form a peristaltic pump.

In accordance with the preferred embodiment of the present invention, aheater is disposed within the substrate. The heater is capable ofheating a blood sample and the array of sensors to a known stabletemperature and maintaining that temperature as the sample is beinganalyzed. Accordingly, fluids that enter the sensor assembly are rapidlyheated due to the small volume and low thermal mass of such fluids.

The sensors of the present invention have very good signal to noiseratio due to a short electrical path length between the sensors andexternal detecting and analyzing electronics within the blood analyzer.Thus, unamplified, low level sensor outputs from the sensors can be useddirectly.

BRIEF DESCRIPTION OF THE DRAWINGS

The objects, advantages, and features of this invention will becomereadily apparent in view of the following description, when read inconjunction with the accompanying drawings, in which:

FIGS. 1a and 1 b are perspective views of a disassembled sensorcartridge in accordance with one embodiment of the present invention.

FIG. 1c illustrates one embodiment of the housing of the presentinvention with a pump tube assembly and a right angle fluid couplinginstalled within the housing.

FIG. 1d illustrates a cartridge in accordance with one embodiment of thepresent invention in which a boss protruding from a blood analyzer mateswith a hollow boss in the cartridge.

FIG. 1e is an illustration of the cartridge cover having an openingthrough which a sensor assembly can be viewed in accordance with oneembodiment of the present invention.

FIG. 2a is an illustration of a blood analyzer in accordance with oneembodiment of the present invention.

FIG. 2b is an illustration of another embodiment of a blood analyzer inaccordance with the present invention.

FIGS. 3a 1-3 a 2 is an illustration of a latch used to mechanicallysecure a cartridge to a blood analyzer in accordance with one embodimentof the present invention.

FIGS. 3b 1-3 b 2 is an illustration of a protective cover in accordancewith one embodiment of the present invention.

FIG. 3c is an illustration of one embodiment of the present invention inwhich barbs extending from a blood analyzer latch a sensor cartridgeinto place.

FIG. 4 is a front plan view of the sensor assembly of the presentinvention.

FIG. 5 is a back plan view of the sensor assembly of the presentinvention shown in FIG. 4.

FIG. 6a is an illustration of one pattern to which a heater conformswhen deposited on a substrate in accordance with the present invention.

FIG. 6b is an illustration of the back side of a substrate after each ofthe dielectric layers have been deposited in accordance with oneembodiment of the present invention.

FIG. 7 is an illustration of the art work used to generate a screen,which in turn is used in the preferred embodiment of the presentinvention to deposit the second layer of conductors and connector pads.

FIG. 8 is an illustration of an oxygen sensor in accordance with thepreferred embodiment of the present invention.

FIG. 9 is a cross-sectional view of a portion of a substrate throughwhich a sensor through hole is formed and on which metal layers of anelectrolyte sensor electrode have been deposited in accordance with oneembodiment of the present invention.

FIG. 10 is a cross-sectional view of one of the hematocrit sensorelectrodes in accordance with one embodiment of the present invention.

FIG. 11 is a cross-sectional view of a sensor showing the first layer ofencapsulant in accordance with one embodiment of the present invention.

FIG. 12 is a cross-sectional view of one of the hematocrit sensorsshowing the first layer of encapsulant in accordance with one embodimentof the present invention.

FIG. 13 is a top plan view of the sensor assembly installed within aplastic encasement.

FIG. 14 is a cross-sectional view of the sensor assembly installed inthe plastic encasement.

FIGS. 15a-15 c illustrate alternative embodiments of the presentinvention in which the relative positions of the sensors differ fromthose shown in FIG. 4.

FIG. 16a is an exploded assembly view of another embodiment.

FIG. 16b is a front elevation view of the cartridge of FIG. 16aassembled X.

FIG. 16c is an end view of the cartridge of FIG. 16b showing theaspiration port in the setracted position X.

FIG. 16d is a view like FIG. 16c showing the aspiration prot in theextended position X.

FIG. 17 is a perpective view of a blood analyzer in accordance with afurther embodiment of the invention.

Like reference numbers and designations in the various drawings refer tolike elements.

DETAILED DESCRIPTION OF THE INVENTION

Throughout this description, the preferred embodiment and examples shownshould be considered as exemplars, rather than limitations on thepresent invention.

Sensor Cartridge

FIGS. 1a and 1 b are perspective views of a disassembled sensorcartridge 100 in accordance with one embodiment of the presentinvention. The sensor cartridge 100 shown in FIGS. 1a and 1 b has fivecomponent parts; (1) a housing 102; (2) a housing cover 104; (3) a pumptube assembly 106; (4) a fluid coupling 108; and (5) a sensor assembly400.

The housing 102 shown in FIGS. 1a and 1 b has a floor 101, four walls103, 105, 107, 109, and an opening 110. Male electrical contact pins1207 of an electrical connector 1205 of the sensor assembly 400 protrudethrough the opening 110. In accordance with one embodiment, theconnector 1205 has a body 116 which also protrudes through the opening110. The walls 118 of the opening 110 generally conform to the shape andsize of the body 116 of the connector 1205. Thus, the sensor assembly400 is constrained from movement in the plane of the floor 101 of thehousing 102. Preferably, the connector body 116 fits loosely within theopening 110. However, in one alternative embodiment of the presentinvention, the body 116 may be friction fit within the opening 116 tomore securely hold the sensor assembly in place during assembly of thecartridge 100. Alternatively, the sensor assembly may be held in placemerely by the forces exerted by the fluid coupling of the sensorassembly 400 to the pump tube assembly 106 and the fluid coupling 108.In yet another alternative embodiment, walls which extend up from thefloor 101 of the housing 102 may be formed to constrain any motion ofthe sensor assembly 400. FIG. 1a shows one such wall 120.

The pump tube assembly 106 preferably comprises a right angle end fluidcoupling 126, a straight end fluid coupling 124, and a pump tube 136. Inaccordance with one embodiment of the present invention, the end fluidcouplings 124, 126 are formed (such as by a conventional moldingprocess) from an elastomer. The fluid coupling 108 may also be formedfrom an elastomer. The fluid coupling 108 is preferably formed as aright angle coupling. That is, the coupling provides a means by which afluid flow path through a first mating fluid coupling may be placed influid connection with a fluid flow path through a second mating fluidcoupling when the fluid flow paths of the first and second coupling areat right angles to one another. The pump tube 136 is preferably veryresilient in order to allow the pump tube 136 to properly interface witha roller to form a peristaltic roller pump, as is described below ingreater detail. A fluid path is formed through the pump tube assembly106 such that fluid enters at one end of the pump tube assembly andexits from the other end.

Walls 122 may be provided to retain the pump tube assembly 106 and fluidcoupling 108 in position within the housing 102. FIG. 1c illustrates oneembodiment of the housing 102 of the present invention with a pump tubeassembly 106′ and a fluid coupling 108′ installed within the housing102. It can be seen that FIG. 1c shows an alternative to the embodimentshown in FIG. 1a and 1 b, in that the end fluid coupling 124′, the rightangle end fluid coupling 126′, and the fluid coupling 108′ shown in FIG.1c are generally rectangular (in contrast with the generally cylindricalshapes shown for the end fluid coupling 124, the right angle end fluidcoupling 126, and the fluid coupling 108 shown in FIG. 1a and 1 b).Hollow cylindrical protrusions from the body of the couplings 108, 108′,126, 126′ have fluid channels therethrough. The fluid channel in eachcoupling 108, 108′, 126, 126′ is at a right angle to a fluid channelalong the longitudinal axis of the each coupling 108, 108′, 126, 126′.Regardless of the shape of the couplings, the protrusions 130, 128 areseated in two openings 132, 134 in the floor 101 of the housing 102(best seen in FIGS. 1a and 1 b). Preferably, the openings are shaped andsized such that the cylindrical protrusions 128, 130 fit snugly withinthe openings 132, 134 and extend just beyond the outer surface of thefloor 101. In either case, a pump tube 136 of the pump tube assembly106, 106′ passes through openings 138 in the housing wall 109.

In accordance with one embodiment of the present invention, ports 1202,1204 of the sensor assembly are directly coupled to the pump tubeassembly 106 and the fluid coupling 108. However, in an alternativeembodiment, an extension tube (not shown) with a fluid channeltherethrough may be provided between the inlet port 1202 and the fluidcoupling 124 or between the outlet port 1204 and the fluid coupling 108.The fluid channel through the extension tube is preferably relativelynarrow to reduce the volume of the sample being analyzed and the amountof calibrant and other fluids used during analysis.

The cover 104 is preferably translucent or clear and has fiveprotrusions 140, 142, 144, 146, 148 which extend upward from the surfaceof the cover 104. Furthermore, as will be described in greater detailbelow, a plastic encasement 1200 (see FIG. 14) is also preferably eithertranslucent or clear. Since the cover and the plastic encasement areeither translucent or clear, the user can view the movement of analytesgas bubbles, and reagents through the sensor assembly within thecartridge. In accordance with one embodiment of the present invention,illustrated in FIG. 1e, the cover 104′ has an opening 170 which allowsthe user of a blood analyzer into which the cartridge is to be installedto view the sensor assembly directly. Accordingly, the user may directlyobserve an analyte gas bubbles and reagents flowing through the sensorassembly.

In one embodiment of the present invention, the protrusions 140, 142,144, 146 align the cover 104 to the housing 102. The protrusion 146 alsoapplies pressure to the top of the sensor assembly 400, together withthe protrusion 148, in order to retain the sensor assembly in positionafter the cover 104 is applied. It will be understood by those skilledin the art that the protrusions may be formed in a wide variety ofshapes in order to align the cover and retain the sensor assembly 400 inplace. Furthermore, in one embodiment of the present invention, no suchprotrusions are provided.

Two reinforced holes 150, 152 are provided through the cover 104. Theholes 150, 152 align with two hollow generally cylindrical bosses 154which extend up from the floor 101 of the housing 102 to acceptretaining devices, such as screws, which secure the cover 104 to thehousing 102. In an alternative embodiment of the present invention,studs extend from the cover in alignment with the bosses 154. Each studfits tightly within the opening in one of the bosses 154 in order tosecure the cover 104 to the floor 101 of housing 102.

In accordance with one embodiment of the present invention, thecartridge of the present invention is assembled by coupling the fluidcoupling 108 to a first port 1204 of the sensor assembly 400. The fluidcoupling 124 is coupled to the other port 1202 of the sensor assembly400. The combination of fluid coupling 108, sensor assembly 400, andpump tube assembly 106 are then lowered into the housing 102 and theprotrusions 128, 130 are inserted into the openings 132, 134. The pumptube 136 is inserted into openings 138 in the wall 109 of the housing102. The cover 104 is then placed over, and secured to, the housing 102.

Once the cartridge 100 is assembled, it may be installed in a bloodanalyzer, such as the blood analyzer 200 illustrated in FIG. 2a. Theblood analyzer of the present invention has a first and second malefluid connector 202, 204 respectively. The first and second male fluidconnectors mate with the cylindrical protrusions 128 and 130 to completea fluid flow path from the first male fluid connector 202, through theright angle end fluid coupling 126 of the pump tube assembly 106, intothe sensor assembly 400, through the inlet port 1202, out the outletport 1204, through the fluid coupling 108, and into the second malefluid connector 204.

Fluids are pumped along the fluid flow path by a peristaltic roller pumpwhich includes a roller 206 that massages the pump tube 136. That is,the pump tube 136 is preferably resilient enough to be stretched overthe roller 206. The roller 206 applies areas of alternating greater andlesser pressure to the pump tube 136, causing those portions of the pumptube 136 that lie over an area of greater pressure to be internallyconstricted and those areas of the pump tube 136 that lie over an areaof lesser pressure to be relaxed to essentially the full unstresseddiameter of the channel through the interior of the pump tube 136. Asthe roller 206 rotates, the areas of alternating greater and lesserpressure traverse the pump tube 136 to generate a peristaltic action inthe pump tube 136.

In addition to the first and second male fluid connectors 202, 204, afemale electrical connector having a plurality of female electricalcontact receptacles are provided on the blood analyzer. The femalereceptacles mate with the male electrical contact pins 1207 of thesensor assembly 400. The first and second male fluid connectors 202, 204preferably extend out further from the blood analyzer than do maleelectrical contact pins from the sensor assembly. Accordingly, themating of the fluid connectors causes the electrical connectors to alignfor mating. In one embodiment of the present invention shown in FIG. 2b,a generally cylindrical boss 208 extends outward from the blood analyzer200′. The boss 208 preferably has a generally ring-shaped groove 210disposed near the distal end of the boss 208.

In accordance with one embodiment of the present invention, a bloodanalyzer 200FIG. 2D is provided with a boss 208. A cartridge 100′ suchas shown in FIG. 1d is provided. The cartridge 100′ has an hollow boss156 located in alignment with the boss 208. The hollow boss 156 of thecartridge has an inner diameter which is slightly larger than the outerdiameter of the boss 208. Four support projections are provided aroundthe periphery of the boss 156. Two of the support projections formgenerally “L-shaped” latch supports 158. The other two supports 160merely provide additional strength to support the boss 156. FIG. 3a isan illustration of a latch 300 which rests on the horizontal edge 162 ofeach latch support 158 and between the upright portions 164 of eachlatch support 158.

A first smaller opening 301 is formed near a proximal end of the latch300. A second larger opening 302 in the latch 300 is sized such that theboss 208 may pass though the second opening 302. At one end of thesecond opening a step 304 is formed. The first opening is sized toaccept a “tooth” 166 which projects upward from a depressed portion 168of the wall 105′, as shown in FIG. 1d. The wall 105′ is cut away fromthe floor 101 of the housing 102 in order to allow that portion of thewall 105′ which is under the tooth 166 to flex inward. Thus, when thelatch 300 is in position between the upright portions 164 of the latchsupports 158 with the tooth 166 engaged with the opening 301, the latchmay be urged inward by applying an inward pressure to the edge 306 ofthe latch 300 which will protrude from the wall 105′. When the cartridge100′ is completely assembled, the cover 104 retains the latch 300 inposition.

When the cartridge 100′ is installed in the blood analyzer 200′, thegroove 210 in the boss 208 engages the step 304 in the latch 300. Thatis, the distance between the edge of the first opening 301 in the latchand the edge of the step 304 is equal to the distance between the inneredge of the tooth 166 and the furthest point of the inner wall of theboss 156 minus the depth of the groove 210 in the boss 208. The width“w” of the step 304 is preferably at least equal to the depth of thegroove 210. Furthermore, the thickness of the step “t” is slightly lessthan the width of the groove 210. Thus, the cartridge 100′ is capturedin the blood analyzer by the engagement of the step 304 in the groove210. By applying inward pressure to the edge 306 of the latch 300, thelatch will move slightly inward as the wall 105′ flexes, thus releasingthe step 304 from the groove and allowing the cartridge 100′ to beremoved from the blood analyzer 200′. It can be seen that all of theconnections between the blood analyzer and the cartridge are preferablymade by moving the cartridge in one direction along a straight linetoward the blood analyzer. Upon proper engagement between the bloodanalyzer and the cartridge, the latch 300 snaps into position, providinga positive audible response to indicate that proper engagement has beenachieved.

In accordance with one embodiment of the present invention, a protectivecover is provided which generally conforms to the shape of the cartridge100. FIG. 3b 1-3 b 2 is an illustration of one such cover. Plugs 350protrude from the cover 352. The plugs 350 are sized to engage theprotrusions 128, 130 in the couplings 108, 126 in order to seal thecouplings when the cartridge is not installed in a blood analyzer.Preferably, each plug 350 fits snugly within the channel through one ofthe protrusions 128, 130. A portion 354 of the cover is extends outwardfrom the cover 354 to support the pump tube 136. A pair of walls 356prevent the cartridge from seating too deeply into the cover 352 andthus prevent the contacts of the electrical connector 1205 fromcontacting the bottom of the cover 352. The cover 352 thus seals thefluid path through the sensor cartridge and covers and protects theelectrical contacts of the sensor assembly 400.

It can be seen from the above description of the cartridge that thepresent invention provides a cartridge that: (1) is very easy toinstall, and thus may be installed with virtually no training; (2)establishes both electrical and fluid connections in one installationprocess with little or no risk of misaligning the electrical or fluidconnections of the cartridge with the corresponding connections of theblood analyzer; (3) includes an integral inexpensive and reliable pumptube assembly; (4) allows the user of the blood analyzer to see themovement of an analyte, gas bubbles, or reagent during analysis; (5) isinexpensive and thus may be disposed of without concern for excessivecost; (6) facilitates rapid, reliable replacement of the sensors of theblood analyzer; (7) reduces contact between blood elements and theanalyzer; (8) is compact in size; (9) can be used for sensors withdifferent analyte panels; and (10) allows one type of analyzer to acceptmany different types of sensors.

It should be understood that the cartridge of the present invention maybe provided in numerous alternative configurations. For example, aplurality of sensor assemblies may be coupled in series to provideredundancy or to increase the number or type of sensors that areprovided within the cartridge. Furthermore, straight fluid couplings mayreplace the right angle fluid couplings, and flexible tubing may be usedto alter the direction of the flow path. Furthermore, the pump tubingmay be directly coupled to the sensor assembly without the need for afluid coupling between the pump tubing and the sensor assembly.Furthermore, a wide variety of latching mechanisms may be used tosecurely latch the cartridge to a blood analyzer. For example, theanalyzer may have resilient barbs. FIG. 3c is an illustration of oneembodiment in which barbs 212 spread apart as each edge of a cartridge100 engages one of the barbs 212. Upon completely installing thecartridge 100, the barbs 212 then return to essentially the sameposition as they maintain without the cartridge with the barbed endslatching the outer surface of the cover of the cartridge. Furthermore, aresilient strap may be stretched across the cartridge to retain thecartridge in engagement with the analyzer 200. Still further, a holethrough the cartridge may be provided to allow a threaded member toengage a tapped hole in the analyzer, thus securing the cartridge to theanalyzer. It will be clear that numerous other alternatives arepossible.

Sensor Assembly

FIG. 4 is a front plan view of one embodiment of the sensor assembly 400of the present invention. FIG. 5 is a back plan view of the sensorassembly 400 of the present invention shown in FIG. 4. The presentinvention is a sensor assembly 400 having a plurality of sensors 403,including highly pure, planar circular silver potentiometric andamperometric electrode sensors disposed on an inorganic substrate 405.The sensor assembly 400 is preferably enclosed within a housing whichdefines a flow cell into which an analyte is transferred for analysis bythe sensors 403. Each sensor 403 is fabricated over a subminiaturethrough hole through the substrate 405. In accordance with the preferredembodiment of the present invention, each subminiature through hole ispreferably laser drilled through the substrate. These through holesreduce the amount of area required on the front side of the substrate byeach of the sensors 403. That is, the present design geometry permits anumber of sensors to be arrayed in a plane with fewer restrictions,since the layers of the conductors do not interfere with the placementof the sensor electrodes. Reducing the required area on the front sideof the substrate allows a relatively large number of sensors 403 to belocated in a relatively small area on the sensor assembly 400, and thusallows the volume of the flow cell to be reduced. Reducing the volume ofthe flow cell reduces the sample size, which is important, since in somesituations many samples are required from the same patient. Furthermore,as a consequence of the small sample size, the low thermal mass of thesensor assembly 400, and the placement of a heater on the back side ofthe substrate, the present invention rapidly reaches a stabletemperature at which analysis can be performed. Accordingly, the presentinvention can be installed into a blood analyzer (not shown) to providerapid results (i.e., approximately 60 seconds in the case of oneembodiment).

In addition to reducing the area required for each sensor 403, the useof subminiature through holes through the substrate under each sensor403 allows the sample and reference solution to be physically isolatedby the substrate 405 from the electrical conductors 410 which transferelectrical charge or current from each sensor electrode to an associatedconnector pad 411 (see FIG. 5). Only the sensor electrodes and athermistor 409 are located on the front side of the substrate. Thepredominant use of the back side of the substrate to route conductorsallows the front side of the substrate (i.e., where space is at a muchgreater premium) to be reserved for those elements which must reside onthe front side (such as the sensor electrodes). It should be noted thatthe conductors 410 and pads 411 are shown using broken lines in FIG. 5to illustrate that an encapsulant 415 is applied over the conductors 410and a portion of the pads 411. As will be discussed in greater detailbelow, solder is deposited over the pads 411 to provide an appropriateelectrical and physical interface to a surface mount connector (notshown in FIG. 5). As will also be described in more detail below, thethermistor 409 (see FIG. 4) is also encapsulated after being depositedon the front of the substrate 405. While the term “deposited” is usedthroughout this document, the meaning is intended to be inclusive of allmeans for forming a structure in a layered device, including screening,plating, thick film techniques, thin film techniques, pressurizedlaminating, photolithographic etching, etc.

In accordance with one embodiment of the present invention, all of theconnections which couple the sensors 403 to external devices aredeposited on the back side of the substrate. These connections arespaced apart to provide the greatest possible insulation resistance. Inone embodiment of the present invention, electrical conductors aredeposited on a plurality of different fabrication layers deposited onthe back side of the substrate 405. No sample or reference solutioncontacts the back side of the substrate, as will be clear from thedescription provided below. A conventional surface mount electricalconnector is preferably mounted on the connector pads to provide anelectrical conduction path through a mechanical interface from thesensors 403 to external devices which detect and process the electricalsignals generated by the sensors 403.

The substrate 405 of the preferred embodiment of the present inventionis essentially impervious to aqueous electrolytes and blood overrelatively long periods of time (i.e., more than six months in the caseof one embodiment of the present invention). In accordance with thepreferred embodiment of the present invention, the inorganic substrate405 is a sheet of approximately 0.025 inch thick commercial grade 96%alumina (Al₂O₃). The substrate 405 is preferably stabilized by a heattreatment prior to purchase. One such substrate is part number 4S200available from Coors Ceramic Company, Grand Junction, Colo.Alternatively, the substrate may be any non-conductive essentially flatsurface upon which the sensors may be deposited, as will be described infurther detail below. For example, the substrate may be any silicon,glass, ceramic, wood product, non-conducting polymer or commerciallyavailable frit that can be used as a substantially smooth flat surface.However, the substrate preferably should be capable of withstanding thepresence of an electrolyte having a pH of more than 6 to 9 and remainingessentially unaffected for an extended period of time (i.e., in theorder of weeks).

Use of an alumina substrate provides the following advantages: (1) lowthermal mass; (2) dimensional stability when subjected to aqueouselectrolytes and blood for extended periods time; (3) establishes amechanically and chemically stable substrate for use with thick filmdeposition techniques; (4) can be accurately laser drilled to highprecision with very small diameter holes; (5) does not react with any ofthe materials which are used to fabricate sensors; and (6) very highelectrical resistance. As a consequence of the fact that the assembly,including the inorganic substrate 405 and each deposited layer, is verystable and does not breakdown when subjected to aqueous electrolytes andblood, the sensor assembly 400 maintains very high isolation between (1)each of the sensors 403; (2) each of the sensors 403 and each electricalconductor; and (3) each of the electrical conductors.

Because the substrate 405 and each of the layers deposited thereon arestable and resists breakdown in the presence of aqueous electrolytes andblood, extremely high electrical resistance is maintained through thesubstrate. Accordingly, the present invention provides very highelectrical isolation between each of the sensors 403, even afterexposure to a corrosive environment over a relatively long period oftime. This is advantageous for the following reasons. In accordance withone embodiment of the present invention, an isotonic reference medium(e.g., a gel or other a viscous solution having a known ionconcentration) is placed over a reference electrode to provide areference for potentiometric sensors which are fabricated on thesubstrate 405. The present sensor assembly 400 can be stored in a sealedpouch (not shown) having a humidity that reduces any evaporation of theisotonic reference medium. Storing the present invention in a sealedpouch having a controlled humidity also ensures that the sensors 403remain partially hydrated during storage. Since the sensors 403 remainpartially hydrated during storage of the sensor assembly 400, thesensors 403 of the present invention require minimal conditioning afterinstallation. Therefore, having the sensors 403 stored in partiallyhydrated state greatly reduces the amount of time the user must waitbefore results can be attained from the sensors 403 of the presentinvention. This differs from prior art sensors which are stored in anessentially dry environment. Such prior art sensors must be assembled orpreconditioned many hours prior to use. It is advantageous to provide asensor assembly 400 which is available for use shortly afterinstallation. For example, blood laboratories which use prior art bloodanalyzers must maintain at least two such prior art blood analyzers orrisk being out of service for many hours after replacement of a sensorassembly (i.e., the time required to assemble, condition, calibrate, andrehydrate the sensors). The sensor assembly of the present invention canoutput results in as little as 10 minutes from the time the sensorassembly is installed, thus reducing the need for a second bloodanalyzer which would otherwise be required as a backup.

In accordance with the sensor assembly 400 shown in FIG. 4 and 5 thefollowing sensors are provided: (1) sodium sensor 403 h; (2) potassiumsensor 403 g; (3) calcium sensor 403 f; (4) pH sensor 403 e; (5) carbondioxide sensor 403 a; (6) oxygen sensor 403 b; and (7) hematocrit valuesensor 403 c, 403 d. A reference electrode 407 is also provided. Thereference electrode is common to each of the potentiometric sensors(i.e., the sodium sensor 403 h, potassium sensor 403 g, calcium sensor403 f and carbon dioxide sensor 403 a sensors) and provides a voltagereference with respect to each such sensor. It will be understood bythose skilled in the art that these sensors, or any subset of thesesensors, may be provided in combination with other types of sensors.

Fabrication of the Sensor Assembly of the Present Invention

The following is the procedure by which one embodiment of the presentinvention is fabricated. It will be understood by those of ordinaryskill in the art, that there are many alternative methods forfabricating the present invention. Accordingly, the description of thepreferred method is merely provided as an exemplar of the presentinvention.

Initially, a series of through holes are drilled through the substrate405. Preferably, each through hole is laser drilled using a CO₂ laser toa diameter in the range of approximately 0.002-0.006 inches as measuredon the front side of the substrate 405. By maintaining the smalldiameter of each through hole, the planar characteristic of an electrodewhich is deposited over the through hole is not distorted by thepresence of the through holes. In the preferred embodiment of thepresent invention, thirteen holes are required, such that one hole isprovided for each sensor, except for the hematocrit sensor 403 c, 403 dand the oxygen sensor 403 b, each of which require two holes. Thehematocrit sensor requires two holes in light of the two electrodes 403c, 403 d. The oxygen sensor 403 b preferably has one through hole forconnection to the cathode of the sensor and one through hole forconnection to the anode of the sensor. In addition, two through holesare preferably used for the connections to the thermistor 409. Also, twothrough holes are preferably used for the reference electrode 407 toreduce the risk of a defective through hole creating an open circuit. Inthe preferred embodiment of the present invention, each through holethat is associated with a sensor electrode is located under the locationat which the associated sensor electrode to be deposited. Each suchthrough hole is preferably located essentially at the center of thesensor electrode with the exception of the oxygen sensor 403 b. However,in an alternative embodiment of the present invention, each through holemay be located anywhere underneath an electrode.

When the substrate 405 is a ceramic material, such as alumina, thesubstrate is preferably annealed after drilling all of the through holesat a temperature in the range of approximately 1000-1400° C., and morepreferably in the range of approximately 1100-1200° C. Annealing thesubstrate after drilling ensures re-oxidation of a nonstoichiometricresidue that attaches to the holes after the laser drilling. Withoutannealing, the residue (which is very reactive) contaminates the sensorelectrodes, resulting in less pure electrode surfaces, which can lead topoor sensor performance. In the preferred embodiment of the presentinvention, the substrate is scribed after annealing. However, in analternative embodiment of the present invention, the substrate may bescribed either before annealing, or not at all. Scribing the substrateallows several individual sensor assemblies formed in the samedeposition processes on one substrate to be separated after all of theassemblies have been completed.

Once the through holes have been drilled and annealed, a thermistorpaste is deposited in a predetermined pattern on the front side of thesubstrate 405 to form a thermistor 409 as shown in FIG. 4. In analternative embodiment of the present invention, the particular geometryof the thermistor may vary from that shown in FIG. 4. In an alternativeembodiment, the thermistor 409 is a discrete component which is notformed directly on the substrate. In the preferred embodiment of thepresent invention, the thermistor paste is part number ESL 2414,available from Electro-Science Laboratories, Inc. The thermistor paste501 is preferably deposited to a thickness of approximately 15-29 μMwhen dried (10-22 μM when fired). The thermistor paste is oven dried andfired at a temperature of approximately 800-1000° C. for approximately1-20 minutes. It will be understood by those skilled in the art that thethermistor 409 may be fabricated with any material that will provideinformation to an external control device by which the temperature ofthe sensor assembly 400 can be controlled. The thermistor is preferablybe placed adjacent to any sensor that is particularly temperaturesensitive or appropriately when measuring a temperature sensitiveanalyte. In an alternative embodiment of the present invention, a numberof sensors and independently controllable heaters may be used toregulate the temperature of each sensor and the local temperature of theanalyte at different locations along the flow path.

Once the thermistor paste has been deposited, dried, and fired, thesubstrate 405 is preferably placed in a vacuum fixture. The vacuumfixture (not shown) has a plurality of vacuum ports, each placed incontact with the opening of a through hole on the front side of thesubstrate. Preferably, each vacuum port is concurrently aligned with oneof the through holes to create a relative low pressure within eachthrough hole of the substrate with respect to the ambient pressureoutside the through holes. A metallic paste, which is preferablycompatible with the metal to be used to form the metallic layer of theelectrodes of the electrolyte sensors 403 h, 403 g, 403 f, as will bedescribed in more detail below, is deposited over the through holes onthe back side of the substrate 405. The deposited metal forms aconductive pad over the through hole. However, due to the vacuum appliedto the front side of the substrate 405, a portion of the metal is drawnthrough the through holes. In accordance with the present invention, themetallic paste is preferably a silver paste, such as part number ESL9912F, available from Electro-Science Laboratories, Inc. In accordancewith the preferred embodiment of the present invention, the metallicpaste is applied through a screen having a mesh density of 250 wires perinch (each wire having a diameter of approximately 0.0016 inches and aspacing of 0.0025 inches) and an emulsion thickness of approximately0.0007 inches. The emulsion is developed to form a mask which allows themetal paste to pass through the screen only at the locations of thethrough holes on the back side of the substrate 405. The metallic pasteis formed by the screen into columns above each through hole. Thosecolumns of metal paste are then drawn down into the through holes by thereduction in pressure caused by the vacuum fixture. This procedure ispreferably performed twice to ensure that each through hole is filledwith the silver paste.

The substrate is then rotated to place the back side of the substrate405 in contact with vacuum ports. The ports are aligned with the throughholes over which the hematocrit electrodes 403 c, 403 d are to bedeposited. The metal with which the front side of the through holes arefilled is preferably selected to be compatible with the particular metalfrom which the electrode to be formed over the through hole is to beformed. In the preferred embodiment of the present invention, thehematocrit electrodes are formed using platinum. Therefore, the metallicmaterial which fills the front side of these through holes and formsconductive pads on the front side of the substrate is preferably asilver/platinum paste, such as a mixture of silver paste, part numberQS175, available from DuPont Electronics, and platinum paste, partnumber ESL 5545, available from Electro-Science Laboratories, Inc. Theuse of a silver/platinum paste presents a compatible interface betweenthe platinum hematocrit sensor electrodes and the silver conductivematerial which fills the back side of the through holes which willunderlie the hematocrit sensor electrodes. The mixture preferably has 50parts silver, and 50 parts platinum. However, in an alternativeembodiment, other alloys of silver and platinum may be used.Furthermore, any alloy which is compatible with platinum (i.e., withwhich platinum forms a solid solution), may be used. In a next screeningprocess, each of the other eleven through holes (i.e., each of thethrough holes except the two over which the hematocrit electrodes 403 b,403 c are to be deposited) are preferably filled from the front side ofthe substrate 405 using the same metallic paste that was previously usedto fill the through holes from the back side of the substrate.Conductive pads, similar to the conductive pads formed on the back sideof the substrate 405, are formed on the front side of the substrate 405.Filling the through holes from both the front and the back side of thesubstrate ensures that the entire through hole will be filled, and thata low resistance electrical contact will be made between the front andback side of the substrate through each through hole.

FIG. 6a is an illustration of one pattern to which a heater 601 conformswhen deposited on the substrate 405 in accordance with the presentinvention. In the embodiment shown, the heater 601 conforms generally toa complex serpentine pattern. FIG. 6a also shows a number ofelectrically conductive traces 603 which provide electrical conductionpaths for current and/or electrical potential to be communicated fromthe electrodes of the sensors 403 to the pins of a connector to beaffixed to the substrate, as will be described in greater detail below.The heater 601 is preferably deposited on the back side of the substrate405. In accordance with one embodiment of the present invention, aheater paste blend including 10 parts of part number 9635-B, availablefrom Heraeus Cermalloy, and 90 parts of part number 7484 available fromDuPont Electronics is deposited to a thickness of 15-33 μM dried (7-20μM fired). In accordance with one embodiment, a through hole vacuum maybe applied to seal any through holes that remain open. It will beappreciated by those skilled in the art that the heater may be anyheater device that provides a source of heat which can be readilycontrolled by a control device that receives information regardingtemperature from the thermistor 409. It will also be appreciated thatthe particular routes taken by the conductors 603 may vary inalternative embodiments of the invention.

Once the heater 601 and conductors 603 have been deposited, a series ofdielectric layers 419 are deposited on the back side of the substrate405 which electrically insulate the heater 601 and the conductors 603from additional layers which are to be later deposited over the heater601 and the conductors 603. The dielectric includes openings throughwhich “vias” can be formed to provide electrical contact paths to theconductors 603 through the dielectric layers. A dielectric paste (suchas part number 5704, available from E.I DuPont) is applied to the backside of the substrate 405, preferably using a conventional thick filmscreening technique. The screen used to apply the dielectric paste masksall locations except those at which a via is to be formed. FIG. 6b is anillustration of the back side of the substrate 405 after each of thedielectric layers 419 have been deposited. It should be noted that theheater 601 and conductors 603 are shown in broken lines to indicate thepresence of the dielectric layer 419 over the heater 601 and conductors603. After two layers of the dielectric paste have been deposited,dried, and fired at a temperature of approximately 800°-950° C., ametallic paste, such as a palladium/silver composite, which in thepreferred embodiment is part number 7484, available from E.I. DuPont, isdeposited over those locations 750 at which vias are to be formed. In analternative embodiment of the present invention, other noble metalmixtures can be used to achieve the desired resistance value within theavailable surface area. The metallic paste is then fired at 800°-950° C.for approximately 1 to 20 minutes. Two more layers of dielectric pasteand metallic paste are deposited, each such layer being fired at800°-950° C. for approximately 1 to 20 minutes directly after beingdeposited. It will be clear to those skilled in the art that othermethods for depositing the dielectric layer and the vias may not requiremultiple layers of dielectric and metal. However, due to limitations onthe thickness of layers which are deposited through a screen, more thanone layer of both dielectric paste and metallic paste are preferablydeposited. The dielectric layers between the conductive lines of theheater 601 build to a height which is nearly equal to the height of thedielectric layer over the heater 601, thus providing a relatively smoothsurface at the back side of the sensor assembly 400.

After the last dielectric layer 419 is deposited, a second layer ofconductors is deposited. FIG. 7 is an illustration of a secondconductive layer, including the second layer of conductors 410, aplurality of connector pads 411, and connections 803 to the resistor 412(see FIG. 5). In one embodiment of the present invention, the secondconductive layer is formed from a metallic paste, such aspalladium/silver, which in the preferred embodiment of the presentinvention is part number 7484 available from E.I DuPont. The secondconductive layer is then oven dried and fired at a temperature in therange of approximately 800°-950° C. for approximately 1 to 20 minutes.The conductors 410 and conductive connector pads 411 complete theconnection between the sensor electrodes and external devices (notshown) coupled to the connector fixed to the connector pads 411. Thesecond layer of conductors is oven dried and fired at a temperature inthe range of approximately 800°-950° C. for approximately 1 to 20minutes.

In accordance with the present invention, conductors 603, 410 aredeposited on only two layers (i.e., the heater layer and the connectorpad layer). However, in an alternative embodiment of the presentinvention in which the geometry of the sensor assembly 400 makes itdifficult to route the conductors from each sensor to an appropriateelectrical contact pad to which a connector is to be electricallycoupled, more than two layers having conductors may be used. In such anembodiment, each such conductor layer is preferably separated by atleast one layer of insulating dielectric material.

After the second layer of conductors has been deposited on the back sideof the substrate 405, each of the layers which form the electrodes ofthe sensors 403 are deposited on the front side of the substrate 405.Concurrent with the deposition of the first metal layer of eachelectrode, contacts 414 to the thermistor 409 are deposited to couplethe thermistor to the through holes that are adjacent the thermistor 409(see FIG. 4). FIG. 8 is an illustration of an oxygen sensor 403 b′ inaccordance with an alternative embodiment of the present invention. Boththe oxygen sensor 403 b and 403 b′ are essentially conventionalamperometric cells. The only difference between the oxygen sensor 403 bshown in FIG. 4 and the oxygen sensor 403 b′ shown in FIG. 8 is theshape of the anodes 701, 701′. In accordance with the preferredembodiment of the present invention, the anodes 701, 701′ areessentially straight conductors which deflect from straight at thedistal end 703, 703′. Preferably, the area of the anode is a minimum of50 times greater than the area of the cathode to ensure the most stableoperation. In addition, the distance between the anode and the cathodeis preferably approximately 0.020-0.030 inches to ensure that thepotential developed across the anode to cathode is not too great. Itshould be noted that the anode of the oxygen sensor may be configured toconform to any number of alternative shapes. These two shapes areprovided merely as exemplars of the shape of the anode in accordancewith two particular embodiments of the present invention. In oneembodiment of the present invention, a metal, such as silver paste, partnumber QS 175, available from DuPont Electronics, is deposited to formthe anode 701, 701′ of the oxygen sensor 403 b′. Alternatively, anymetal suitable for use in forming the anode of an amperometric cell maybe used, such as platinum, ruthenium, palladium, rhodium, iridium, gold,or silver. A distal end 703, 703′ of the anode 701, 701′ is depositedover one of the above described through holes 705 through the substrate403.

The cathode conductor 707 is then deposited. A distal end 709 of thecathode conductor 707 is deposited over another of the through holes 711through the substrate 403. The cathode conductor 707 and the anode 701,701′ are oven dried and fired at a temperature of approximately 800° C.to 950° C. for approximately 1 to 20 minutes.

FIG. 9 is a cross-sectional view of a portion of the substrate 405through which a sensor through hole 702 is formed and on which metallayers of an ion sensitive sensor electrode have been deposited.Concurrent with the deposition of the oxygen sensor 403 b, and bydeposition of the same type of material (preferably silver) deposited toform the metallic layer of the anode 701, 701′ of the oxygen sensor 403b, a first metallic layer 704 of each of the electrodes associated witheach of the other sensors 403 a, 403 e-403 h and the reference electrode407 are deposited on the substrate over a through hole 702. In the caseof sensors 403 a, 403 e-403 h which are to have a polymeric membranedisposed over the metallic layer, a second metallic layer 706,preferably of the same material as the first metallic layer 704, isdeposited over the first metallic layer 704 in order to reduce anydistortion in the flatness of the surface due to the presence of thethrough hole 702 located beneath the first metallic layer 704. That is,electrodes formed over a through hole 702 with only one layer ofmetallic material tend to develop a depression over the through hole702. Such a depression is generally of no consequence if the electrodeis not to be coated with a polymeric membrane.

However, in sensors which have polymeric membranes, such a depressioncan cause the membrane to become embedded in the electrode 704. As aresult of this distortion, optimal performance would not be achieved.That is, very uniform membrane geometry is important to achievingoptimal sensor function and performance. This can be understood in lightof the fact that in the preferred embodiment of the present invention,the thickness of a polymeric membrane that is applied over the metalliclayers 704, 706 is determined by pouring a controlled volumetricquantity of a membrane solution into a sensor cavity having well defineddimensions (as will be discussed further below). The membrane formedover the metallic layer 706 is very thin (i.e., approximately 5-250 μM).Any variation in the thickness of the membrane at one point, effects thethickness of the membrane at each other point. Such variations in thethickness of the membrane adversely effect the performance of the sensor403. Therefore, if a depression exists in the metallic layer whichunderlies the polymeric membrane, the membrane will be thicker over thedepression, and thus thinner over the remainder of the electrode.Depositing a second metallic layer 706 smooths any such depression whichmight otherwise exist. The second metallic layer 706 preferably has adifferent diameter than the first layer 704 in order to reduce thechances that the metallic layers will puncture the polymeric membranedue to the abrupt edge that would be formed at the perimeter if both thefirst and second metallic layers 704, 706 were to have the samediameter. Since the presence of a depression is insignificant inelectrodes of sensors which do not require a thin membrane, thesesensors are preferably formed having only one metallic layer 704.

The preferred dimensions for the metallic layers 704, 706 of each sensorin accordance with one embodiment of the present invention are providedbelow. It will be understood by those skilled in the art that otherdimensions may be quite suitable for fabricating sensors. However, thedimensions presented reflect a tradeoff between reduced impedance andreduced size. A tradeoff is required because of the desire to form thesensor in as small an area as possible, and the competing desire to forma sensor which has a relatively low impedance. These two goals areincompatible because of the inverse relationship between size andimpedance. That is, in general, size is inversely proportional toimpedance. Therefore, the greater the size of the sensor electrode, thesmaller the impedance of that electrode.

The diameter of the first metallic layer 704 of the CO₂ sensor 403 a,the pH sensor 403 e, and each of the electrolyte sensors 403 f, 403 g,403 h is 0.054 inches. The diameter of the second electrode layer 706 ofeach of these sensors is 0.046 inches. The second layer 706 is depositedover the first layer 704. The metallic layer 704 of the referenceelectrode is generally rectangular, having rounded comers with radiusequal to one half the width of the electrode. The width of the electrodeis preferably 0.01 inches, and the length is preferably 0.08 inches. Itwill be understood by those skilled in the art that the referenceelectrode 407 may be formed in numerous other shapes. After the firstmetallic layer 704 is deposited, the substrate 405 is oven dried andfired at approximately 800°-950° C. for approximately 1-20 minutes.After deposition, the second metallic layer 706 is similarly dried andfired. Each of the metallic layers 704, 706 is preferably 16-36 μM thickafter drying, and 7-25 μM thick after firing.

FIG. 10 is a cross-sectional view of one of the hematocrit sensorelectrodes 403 c. Only one of the two electrodes 403 c, 403 d are shown,since each are essentially identical. In accordance with the preferredembodiment of the present invention, the metal used to form theelectrodes of the hematocrit sensor 403 c, 403 d differs from the metal704, 706 used to form the electrodes of the electrolyte sensors 403 f,403 g, 403 h, the pH sensor 403 e, the oxygen sensor 403 a, and thereference electrode 407. Therefore, in the preferred embodiment, theelectrodes of the hematocrit sensor 403 c, 403 d are formed bydepositing a third metallic layer 1001. Since no polymeric membrane isto be placed over the metallic layer 1001 of the hematocrit electrodes403 c, 403 d, the hematocrit electrodes 403 c, 403 d preferably onlyhave one metallic layer. In the preferred embodiment of the presentinvention, the metal used to form the electrodes for the hematocritsensor 403 c, 403 d is a cermet platinum conductor, such as part numberESL 5545, available from Electro-Science Laboratories, Inc. The diameterof the metallic layer 1001 of each hematocrit sensor electrode is 0.054inches. The hematocrit sensor electrodes 403 c, 403 d are preferablyspaced approximately 0.15 inches apart.

After forming the metallic layer 1001 of the hematocrit sensorelectrodes 403 c, 403 d, the cathode conductor 707 (see FIG. 8) isdeposited. In accordance with the preferred embodiment of the presentinvention, the cathode conductor 707 is formed from a gold paste, suchas part number ESL 8880H, available from Electro-Science Laboratories,Inc. It will be understood by those skilled in the art that the cathodeconductor 707 may be fabricated from any metal commonly used to form acathode of a conventional amperometric cell, However, it should be notedthat the level of contaminants in the paste will effect the sensorcharacteristics. Furthermore, in an alternative embodiment of thepresent invention the particular geometry of the cathode conductor 707may vary from that shown in FIG. 8. At the same time that the cathodeconductor 707 is deposited, a pair of laser targets 417, 418 arepreferably deposited. The laser targets 417, 418 provide a referencewhich is used to form a cathode 717, as will be discussed in greaterdetail below. Once deposited, the cathode conductor 707 is dried andfired at a temperature of 800°-950° C. for approximately 1 to 20minutes.

Once the cathode conductor 707 has been dried and fired, a resistor 412is preferably deposited on the back side of the substrate 405, as shownin FIG. 5. The resistor 412 is coupled in series with the heater 601 inorder restrict the current to an appropriate level through the heaterduring electrical conduction. Next, a first layer of an encapsulant isdeposited on the front side of the substrate 405. FIG. 11 is across-sectional view of a sensor 403 showing the first layer ofencapsulant 901. FIG. 12 is a cross-sectional view of one of thehematocrit sensors 403 c showing the first layer of encapsulant 901. Itshould be noted that FIGS. 10 and 11 are not to scale and that the firstlayer of encapsulant 901 is preferably very thin (i.e., preferably onlya few microns). The encapsulant 901 is deposited essentially over theentire front side of the substrate 405 in order to prepare the surfaceof the substrate to receive a polymer, as will be discussed in moredetail below. In accordance with the preferred embodiment of the presentinvention, the encapsulant 901 is deposited through a screen using aconventional thick film technique. The screen preferably has a densityof 250 wires per inch (with a wire diameter of approximately 0.0016),and an emulsion thickness of 0.0007 inches. The screen masks theencapsulant 901 from forming over the thermistor 409 and metallic layers704, 706 of each of the sensors. However, in the preferred embodiment,the distal end 703, 703′ of the anode 701, 701′ and the entire cathodeconductor 707 are encapsulated, as shown for example in FIG. 8. A highquality encapsulant is preferably used which will not undergo chemicalalteration in the presence of a caustic solution (such as blood or otheraqueous solvents). For example, in the preferred embodiment, theencapsulant is part number ESL 4904, available from Electro-ScienceLaboratories, Inc. However, the thermistor 409 is preferably notencapsulated with the higher quality encapsulant, since such highquality encapsulants typically require firing at high temperatures (850°C., for example in the case of encapsulant used in the preferredembodiment). Such high temperatures will cause the thermistor 409 todeform. Therefore, only after firing the high quality encapsulant canthe thermistor be encapsulated. Accordingly, in the preferred embodimentof the present invention, the thermistor 409 is encapsulated with anencapsulant which may be fired at a low temperature.

In the preferred embodiment of the present invention, a second layer ofencapsulant 905 is deposited only over the cathode conductor 707 inorder to ensure that the cathode conductor is securely isolated. In oneembodiment of the present invention, the second layer of encapsulant 905is applied in two screening procedures in order to provide a totaldesired thickness for both the first and second layers of encapsulant ofapproximately 27-47 μM. While alternative embodiments of the presentinvention may employ an encapsulant layer which differs in thickness, athickness in the range of approximately 27-47 μM provides satisfactoryisolation of the cathode conductor 707. Furthermore, i single layer ofencapsulant provides sufficient treatment of the surface of thesubstrate 405 to allow a polymer to be deposited and bonded to thesubstrate 405, as further explained below.

After the encapsulant 901, 905 are deposited over the cathode conductor707, a hole is preferably laser drilled through the encapsulant 901, 905to expose a portion of the cathode conductor 707, and thus form thecathode 717. The cathode may be laser drilled either before or afterfiring the encapsulant. The laser targets 417, 418 are used to visuallyalign the laser apparatus in order to drill the hole at the correctlocation. That is, the lower horizontal edge of the target 417identifies a line in the horizontal direction. Likewise, the leftmostedge of the laser target 418 identifies a line in the verticaldimension. The cathode is then formed at the intersection of these twolines. Alternatively, the cathode 717 is formed by masking a portion ofthe cathode conductor 707 in order to prevent the encapsulant 901 fromforming over that portion of the cathode conductor 707. In yet anotherembodiment of the present invention, the cathode 717 may be exposed by achemical etch. It will be clear to those skilled in the art thatnumerous other methods may be used to expose a portion of the cathodeconductor 707 in order to form a cathode 717.

After applying the first and second encapsulant layers to the front ofthe substrate 405, a thermistor encapsulant 413 is deposited over thethermistor 409. The thermistor encapsulant 413 can be fired at arelatively lower temperature (such as approximately 595° C.) and thusfiring of the thermistor encapsulant 913 does not disturb the geometryof the thermistor 409. In one embodiment of the present invention, thethermistor encapsulant 413 is applied in two screenings in order toachieve a desired thickness and to ensure that no pores are formed inthe encapsulant 413. It will be understood by those skilled in the artthat the encapsulant over the thermistor 409 should remain relativelythin in order to avoid adding any delay in the sensing of thetemperature of the sensor assembly 400. In addition, a resistorencapsulant 415 is deposited over the resistor 412 on the back side ofthe substrate 405. The resistor encapsulant 415 is preferably the samematerial as the thermistor encapsulant 413.

After the resistor encapsulant 413 has been deposited on the back sideof the substrate 405, a first polymer layer 1101 is deposited on thefront side of the substrate 405. The first polymer layer (together withthe first encapsulation layer 901) forms the lower wall 902 of aplurality of sensor cavities 903 (see FIGS. 10 and 11). The polymer ofthe preferred embodiment of the present invention is screen printable,absorbs minimal moisture, chemically isolates the membrane chemistriesof adjacent cavities, and produces a strong solution bond with thepolymeric membrane also forms a strong bond with the dialectic layerswhen exposed at the inside surface of the cavity by an appropriatesolvent (such as tetrahydrofuran, xylene, dibutyl ester, and carbitolacetate or any cyclohexanone solvent) in the membrane formation, as willbe discussed in further detail below.

The polymer used to form the layer 1101 is preferably a composition of28.1% acrylic resin, 36.4% carbitol acetate, 34.3% calcined kaolin, 0.2%fumed silica, and 1.0% silane, noted in percentage by weight. Theacrylic resin is preferably a low molecular weightpolyethylmethacrylate, such as part number 2041, available from DuPontElvacite. The calcined kaolin is preferably a silaninized kaolin, suchas part number HF900, available from Engelhard. The silane is preferablyan epoxy silane, such as trimethoxysilane. Silane bonds to the hydroxylgroups on the glass encapsulant over the substrate, and yet is left witha free functional group to crosslink with the resin's functional group.In accordance with one embodiment of the present invention, the firstpolymer layer 1101 is deposited in three screening processes in order toattain the desired thickness (i.e., preferably approximately 0.0020inches). The first polymer layer is dried after each screening process.A second polymer layer 1103 is deposited to form an upper wall 904 ofthe sensor cavities 903. The first and second polymer layer 1101, 1103differ only in the diameter across the cavity at the lower cavity wall902 and at the upper cavity wall 904 and the number of screeningprocesses that are required to achieve the desired depth. In the case ofthe second polymer layer, 10 screening procedures are performed. Thesecond polymer layer is dried after each screening procedure. Inaddition, after the last two procedures, the polymer is both screenedand cured. In the preferred embodiment of the present invention, thelast screening procedure may be omitted if the second polymer layer hasachieved the desired thickness (i.e., preferably 0.0075-0.0105 inchesafter curing).

The diameter of the cavities are preferably carefully controlled to aidin controlling the deposition of the membranes which are placed over theelectrodes of the sensors (i.e., the shape and thickness of themembranes). That is, the sensor cavities enable a droplet of polymericmembrane solution to be captured and formed into a centrosymmetric formover the electrode with sufficient surface contact with the walls of thecavity to assure that the membrane remains physically attached.

Preferably, the sensor cavities 903 for the pH sensor 403 e, theelectrolyte sensors 403 f, 403 g, 403 h, and the hematocrit sensor 403c, 403 d, each have a total depth of approximately y=0.0075 inches, adiameter at the upper wall 904 of approximately x₁=0.070 inches, and atthe lower wall of approximately x₂=0.06 inches (see FIG. 1l). Thediameter x₃ of the carbon dioxide sensor cavity 903 is slightly largerthan the diameter x₁ of the electrolyte sensors 403 e-403 f and thehematocrit sensor electrodes 403 b, 403 c. In the preferred embodiment,the diameter X₃ is equal to 0.078 inches (see FIG. 12). It should beunderstood that a membrane of the same thickness may be produced byincreasing the diameter of the sensor cavity 903 and increasing thevolumetric quantity of the membrane solution that is applied to thesensor in proportion to the increase in the volume of the cavity.Likewise, the same thickness can be maintained by decreasing thediameter of the sensor cavity 903 and proportionally decreasing thevolumetric quantity of the membrane solution. It will be clear to thoseskilled in the art that in an alternative embodiment of the presentinvention, the sensor cavities may have a shape other than the generallycylindrical shape disclosed above. For example, in accordance with oneembodiment of the present invention, the electrodes are formed in anoval shape to reduce the required volume of a sample. However, in thepreferred embodiment, the sensor cavities are either cylindrical orgenerally conical.

Once the sensor cavities 903 have been formed and the polymer layersdried, each silver potentiometric electrode is chemically chlorodized tocreate a layer of silver chloride. The cavity 903 of each ion sensitivesensor is filled with an electrolyte which is appropriate to theparticular type of sensor 403. In the preferred embodiment of thepresent invention, the electrolyte used in the sodium, potassium andcalcium electrolyte sensors are ions of inorganic salts thatdisassociate in solution, such as NaCl, KCl, or CaCl₂. In accordancewith one embodiment of the present invention, the electrolyte solutionis evaporated to a solid form. Alternatively, the electrolyte remains aliquid or a gygroscopic water insoluble gel that acts as a support toimmobilize the electrolyte. In accordance with one embodiment of thepresent invention, such a gel may crosslinked after transfer to thecavity 903. Furthermore, in accordance with one embodiment, the gelundergoes polymerization by a catalyst contained within the solution. Inone such embodiment, the gel is polymerized by activating a catalystwith heat or radiation.

The gelled polymer is preferably one of the following, or a mixture ofthese: (1) starch, (2) polyvinyl, (3) alcohol, (4) polyacrylamide, (5)poly (hydroxy ethyl methacrylate), or (6) polyethylene glycol orpolyethylene oxide ether, or another long chained hygroscopic polymer.Hygroscopic polysaccarides or natural gelatin are preferably added tothe electrolyte solution.

The electrolyte used in the pH sensor preferably has an acidic pH in therange of about 3-7. In accordance with one embodiment, the electrolyteis an aqueous solution of potassium hydro phosphate (KH₂PO₄), preferablyhas 13.6 grams of potassium hydro phosphate in one liter of deionizedwater. The electrolyte suppresses the reaction of carbon dioxide andwater to minimize the extent to which the carbon dioxide influences thepH of the electrolyte. This favors the pH response for pH measurementand minimizes the response of CO₂. The electrolyte for pCO₂ sensor isinitially at an alkaline in the range of approximately 7-14. However, inthe preferred embodiment of the present invention, the electrolyte isapproximately 8 due to the presence of bicarbonate ions. In accordancewith the present invention, the electrolyte for the pCO₂ sensor ispreferably 0.02 moles of sodium bicarbonate in a liter of deionizedwater. Solutions in either liquid or gel phase may be used. A sensorwhich includes such an electrolyte is also described in U.S. Pat. No.5,336,388, assigned to PPG Industries, Inc, which is incorporated in itsentirety by this reference.

The electrolyte of the oxygen sensor 403 a provides a low impedancecontact across the anode and cathode and not to create a standardchemical potential as is the case in the aforementioned potentiometricsensors. Suitable electrolytes are NaCl and KCl. The electrolyte may beeither a fluid or a gel. The preferred use of the electrolyte is in abuffered solution such as one having 0.1 mole potassium hypophosphite(KH₂PO₃).

All of the aforementioned electrolytes are preferably encapsulated by aselectively permeable, hydrophilic membrane that serves to trap theelectrolyte against the electrode. Such membranes include a polymer, aplasticizer, an ionophore, a charge screening compound, and a solvent.The membranes are selective permeable barriers that restrict the freepassage of all but the desired ion. The membrane preferably comprises aninert iypophilic polymer dispersed in an organic plasticizer.

Water molecules will rapidly diffuse across these membranes. Inaccordance with one embodiment of the present invention, the inertpolymer is polyvinlychoride (PVC). However, in an alternativeembodiment, other ion permeable polymers may be used, such as (1)copolymeric vinyl ethers, (2) porous polytetraflourethelene (PTFE), (3)silicones, (4) cellulose acetate, (5) poly (methlymethacrylate), (6)polystyrene acrylate, (7) methacrylate copolymers, (8) polyimides, (9)polyamides, (10) polyurethanes, (11) polybisphenol-A carbonate(polysiloxane/poly(bisphenol-A carbonate) blocked copolymer, (12)poly(vinylidenechloride); and (13) lower alkyl acrylate and methacrylatecopolymers and polymers. It will be clear to those skilled in the artthat this list is not exhaustive, and that other such ion permeablepolymers may be used.

Furthermore, suitable plasticizers include (1) dioctyl adipate, (2)bis(2-ethylhexyl)adipate, (3) di-2-ethlylhexyladipate, (4) dioctylphthalate, (5) 2-nitrophenyl octyl ether (NPOE), (6) diotcyl sebacate,(7) nitrobenzene, (8) tri(2-ethylhexyl) phosphate, (9) dibutyl sebacate,(10) diphenyl ether, (11) dinonyl phthatlate, (12) dipenyl phthalate,(13) di-2-nitrophenyl ether, (14) glycerol triacetate, (15) tributylphosphate, (16) dioctyl phenyl phosphate, and similar long chainedethers and hydrocarbons, and combinations thereof. In the preferredembodiment, a combination of bis(2-ethylhexyl)adipate,2-nitrophenyloctylether or 0-nitrophenyloctylether (NPOE), andnitrobenzene are used as the plasticizer for the pH and CO₂ sensor.Dioctyl Phthalate is preferably used as the plasticizer in the calcium,potassium and sodium sensors.

The membrane polymer and plasticizers are preferably soluble in organicsolvents, such as cylohexanone, tetrahydofuran, xylene, dibutyl ester,and carbital acetate. In accordance with one embodiment of the presentinvention, such solvents are removed from the membrane after applicationover the electrode by vacuum drying at ambient temperatures or lowtemperatures less than 100° C. The solvent softens the organic layer onthe substrate that supports the membrane and encapsulates the internalelectrolyte over the electrode while allowing penetration of themembrane by the ion via the complexing agent or ionophore. In accordancewith one embodiment of the present invention, after encapsulation, theinternal electrolyte is hydrated for a predetermined period prior to useto allow water vapor to permeate the membrane and form an internalelectrolyte solution producing a chemically and physically uniformdistribution of charge on the electrode.

It will be understood by those skilled in the art that any ionophore orion exchanger that mediates the interaction of the ion with environmentand which facilitates the translocation of the ion would be suitable foruse in the membrane of the present invention. For example, in thepresent invention the ionophore or ion exchanges may be another of thefollowing: (1) tridodecylamine (TDDA), (2) tri-n-dodecylamine, (3)valinomycin (K⁺); (4) methyl monesin (Na⁺), or (5)tridodecylmethyl-ammonium chloride (Cl⁻). A lipophilic organic anionserves as a balancing specie, such as tetraphenyl borate is preferablypresent to provide electroneutrality. The membranes of the presentinvention provide accurate detection and fast response over long periodsof use.

The oxygen sensor membrane restricts access of electroactive materialsother than oxygen to the electrode surface while allowing free diffusionof oxygen to the electrode surface.

All membrane solutions arc dispenses in the sensor cavities usingautomated fluid dispensing systems. These systems have three main parts:(1) a horizontal x-y-z motorized and programmable table (such as thoseavailable from Asymtek of Carlsbad, Calif.); (2) a precision fluidmetering pump (such as those available from Fluid Metering, Inc. ofOyster Bay, N.Y.); and (3) a personal computer control unit. All threeparts are linked by a digital communication protocol. Software forset-up and dispensing a sequence of liquid microvolumes communicates thex, y, and z positions to the table, and timing of the dispensing pumpcontroller. At each cavity, the metering pump transfers a preset volumeof electrolyte or membrane solution through fine diameter tubing from asupply reservoir to a needle or nozzle mounted on the motorized axes ofthe table and then to the cavity. The fluid may be successfullydispensed with a number of different pumps; pinch tube, rotary positivedisplacement or diaphragm valves. The drop size is generally no largerthan one diameter of the sensor cavity.

After dispensing the aqueous or organic solution, the membrane is formedby drying or curing liquid. Drying removes the solvent components byevaporation. The drying process may be performed by heating or applyinga vacuum pressure. Some organic solutions may be cured either thermallyor by exposure to ultra-violet radiation.

The combination of the geometry, membrane composition, and aqueous ororganic internal electrolyte have been found to yield membranes ofminimal thickness, with controlled diffusion paths so thatpotentiometric sensor to a varying concentration of gas. Elimination ofin-plane electrical connections to the electrode by use of asubminiature through hole assures better control of the electro-chemicalprocess. In addition, the use of subminiature through holes improves theflatness of the bonding surface of the polymer coating laminated on thesubstrate for better bonding and sealing of the flow cell.

FIG. 13 is a top plan view of the sensor assembly 400 installed within aplastic encasement 1200. FIG. 14 is a cross-sectional view of the sensorassembly 400 installed in the plastic encasement 1200. After each of thesensors have been completed, the pads 411 are plated with solder. Thesolder provides an electrical and mechanical interface between the pads411 and contacts 1209 of a conventional electrical surface mountconnector 1205. The contacts 1209 of the surface mount connector 1205are soldered to the pads 411 in a conventional manner. In addition, theconnector 1205 is preferably secured to the substrate 405 by anadhesive, such as an epoxy glue. Electrically conductive pins 1207 ofthe conventional connector 1205 permit the sensor assembly 400 to beeasily installed and in, and removed from, a blood analyzer (not shown).Use of a conventional surface mount connector 1205 result in a reliableinterface to the blood analyzer instrumentation, provides a simpledesign, low cost construction, an simple test interface, and allowscritical connections to be spaced apart to ensure high electricalresistance between each critical connection. Furthermore, theconventional surface mount connector 1205 allows the present inventionto be mass produced at low cost, and makes the present inventionanalogous to familiar semiconductor dual-in-line packages.

The front side of the sensor assembly 400 is enclosed in the plasticencasement 1200 which forms a flow cell 1201 and a reference cell 1203.A lap joint 1211 is preferably formed between the sensor assembly 400and the encasement 1200. In accordance with the preferred embodiment ofthe present invention, an adhesive, such as epoxy glue, is used tosecure the sensor assembly 400 in the encasement 1200. The encasement1200 is formed with inlet and output ports 1202, 1204, respectively. Theinlet and outlet ports 1202, 1204 allow a sample to be injected into,and discharged from, the flow cell 1201. The adhesive seals thereference cell 1203 and the flow cell 1201 along the lap joint, suchthat fluid can only enter and exit through the inlet and outlet ports1202, 1204.

The encasement is preferably formed of a material having low oxygenpermeability, low moisture permeability which is transmissive toultraviolet radiation, and which is resistant to color change uponexposure to ultraviolet radiation, such as a composition of acrylic,styrene, and butadene. Because even the preferred composition absorbsoxygen, the encasement 1200 is preferably formed with a third cell 1213.The third cell 1213 reduces the amount of encasing material which isadjacent to the flow cell 1201. However, it will be clear to thoseskilled in the art that such a third cell 1213 is not necessary for theproper operation of the present invention. In addition, in oneembodiment of the present invention the amount of encasing material isreduced to a minimum to reduce the absorption of oxygen from a samplewhich is present in the flow cell 1201.

The flow cell 1201 is formed to ensure that a sample which enters theflow cell comes into contact with each of the sensors 403. Furthermore,the flow cell 1201 is very shallow, thus the volume of the flow cell1201 is very small (i.e., 0.05 milliliters in the preferred embodiment).A very thin reference channel 1206 (preferably 0.005-0.010 inches indiameter) between the reference cell 1203 to the flow cell 1201 provideselectrical contact between the reference medium which resides within thereference cell 1203. The reference medium may be any well knownreference electrolyte in solution or gel form. However, in the preferredembodiment, the reference medium is preferably a natural polysaccharide,such as agarose, gelatin, or polyacrylamide. The greater viscosity ofthe reference medium used in the preferred embodiment retardsevaporation of the reference medium, as well as preventing the referencemedium from intermingling with the fluids in the flow cell 1201. Thereference medium is preferably introduced into the reference cell 1203after the sensor assembly 400 is installed in the encasement 1200. Inaccordance with the present invention, a vacuum is created in the flowcell 1201 and the reference cell 1203 by applying a low pressure sourceto either the inlet or outlet port 1204, 1206. The reference medium isthen applied to the other port 1206, 1204. Preferably, the referencemedium is heated to approximately 37°-50° C. by the heater 601 or byapplication of heat through an external heat source to reduce theviscosity of the reference medium, and thus allow the reference mediumto completely fill the reference cell 1203. Once the gel has filled thereference cell 1203, any excess reference medium is gently flushed fromthe flow channel prior to allowing the reference medium to cool. In analternative embodiment of the present invention, the viscosity of thereference medium may be increased in response to a chemical reactionbetween the medium and a catalyst which is placed into the referencechannel either before or after the reference medium.

It should be noted that when the height of the fluid column over thesensor array has been minimized to conserve sample volume (0.10 inches,for example), measurement is preferably made within 10-15 seconds afterthe sample has entered the flow cell 1201.

It will be seen from the above description of the present invention,that the sensors are not separable into parts, but rather form a signalmodular unit, designed for a predefined life, installed once, and thendiscarded. Discarding the unit is economically feasible due to the lowcost at which such sensor assemblies can be fabricated. The presentinvention makes it possible to provide a low cost system which is builtaround standardized electronic assemblies by providing a low cost, massproducible sensor assembly that has highly accurate and reproducibleresults.

It should be clear to those skilled in the art that the use ofsubminiature through holes to route electrical signals from theelectrodes of the sensors to the opposite side of the substrate allow achemically selective membrane overlaying the planar electrode tofunction with the desired sensor reaction mechanism while providing ameans for packing a number of sensors into a relatively small area onthe surface of the substrate. The use of the subminiature through holesalso allows for excellent physical isolation of the sample from theconductors that carry the electrical signals between the sensorelectrodes and the instrumentation used to process those signals. Thisphysical isolation results in very high electrical isolation betweensignals generated by each of the sensors

FIGS. 15a-15 c illustrate three alternative embodiments of the presentinvention in which the relative positions of the sensors differ fromthose shown in FIG. 4.

New Sensor Cartridge

FIG. 16a is an assembly views of a disassembled sensor cartridge 1600 inaccordance with another embodiment of the present invention. The sensorcartridge 1600 shown in FIG. 16a has four of the four basic componentparts as in the previous embodiment; (1) a housing 1602; (2) a housingcover 1604; (3) a pump tube assembly 1606; (4), a sensor assembly 400,the same as in the prior embodiment; and (5) a novel direct input fluidaspiration port assembly 1608. This new cartridge has a direct inputaspiration port 1608 wherein the fluid sample is introduced directlyinto the cartridge rather than routed through the analyzer as in theprior embodiment. The sensor 400 is rotated or turned around one hundredeighty degrees in the cartridge showing from its position in the priorembodiment so that the pump tube assembly 1606 is connected to thesensor outlet 1204 rather than the inlet as in the prior embodiment.

The housing 1602 shown in FIGS. 16a and 16 b is similar in many respectsto the prior embodiment and has a floor 1601, four walls 1603, 1605,1607, 1609, an opening 1610, and in addition, a construction on one endfor mounting the articulated intake aspiration stylus. Male electricalcontact pins 1207 (FIG. 1a) of an electrical connector 1205 of thesensor assembly 400 protrude through the opening 1610. The walls of theopening 1610 generally conform to the shape and size of the body of theconnector 1205FIG. 1b. Thus, the sensor assembly 400 is constrained frommovement in the plane of the floor 1601 of the housing 1602. Preferably,the connector body 1616 of the sensor assembly fits loosely within theopening 1610.

The pump tube assembly 1606 is substantially as in the prior embodimentand preferably comprises a right angle end fluid coupling 1626, astraight end fluid coupling 1624, and a pump tube 1636. In accordancewith one embodiment of the present invention, the end fluid couplings1624, 1626 are formed (such as by a conventional molding process) froman elastomer. The pump tube 1636 is preferably very resilient in orderto allow the pump tube 1636 to exit and enter the housing at openings1638 and properly interface with a roller to form a peristaltic rollerpump, as is described below in greater detail. A fluid path is formedthrough the pump tube assembly 1606 such that fluid enters at one end ofthe pump tube assembly and exits from the other end. Walls 1622 may beprovided to retain the pump tube assembly 1606 in position within thehousing 1602.

The direct input aspiration port assembly 1608 includes a rotatablefluid coupling which in one embodiment comprises a tube 1640 mounted inand extends through a body 1642 and mounts in a flexible or elastomerictube 1644 at the end of sensor assembly 400. The tube 1644 flexes toallow rotation of the tube 1640 up to about 90 degrees. The inputaspiration port assembly 1608 is preferably formed as a right anglecoupling with the major portion of tube 1640 at right angle to the endmounted in tube 1644 and the pivot or rotating axis. That is, thecoupling provides a means by which tube 1640 rotates or pivots throughabout 90 degrees from a recessed positioned as shown FIG. 16c to aposition extending outward from the surface of the housing as shown inFIG. 16d. The housing 1602 is provided with a wall 1615 parallel to wall1603 and aligned openings 1616 which journal the pivoting body 1642. Theparallel walls also form a recess 1617 into which the aspiration tube orstylus 1640 is normally recessed. The housing is also formed with anextension 1618 which forms a recess for an actuating lever or tab 1619for manually rotating the aspiration tube 1640. A slot 1621 is formed inthe extension 1618 to allow a tab 1625 on the back of lever 1619 toextend and retract and to activate some signal such as a switch or blocka light beam to prevent operation. The tab can block a signal such as alight beam to or from a source or sensor 1627. A removable protectiveelastomeric cap 1623 covers the inlet end of tube 1644. In accordancewith one embodiment of the present invention, port 1204 of the sensorassembly is directly coupled to the pump tube assembly 1606. The inletport 1202 of the sensor assembly 400 is coupled to the input aspirationport assembly 1608. The cover 1604 is preferably translucent or clearand has a transparent window to enable viewing of the sensors.Furthermore, as will be described in greater detail below, a plasticencasement 1200 (see FIG. 14) is also preferably either translucent orclear. Since the cover and the plastic encasement are either translucentor clear, the user can view the movement of analytes gas bubbles, andreagents through the sensor assembly within the cartridge. In accordancewith one embodiment of the present invention, illustrated in FIG. 16b,the cover 1604 has an opening 1670 which allows the user of a bloodanalyzer into which the cartridge is to be installed to view the sensorassembly directly. Accordingly, the user may directly observe an analytegas bubbles and reagents flowing through the sensor assembly.

Two reinforced holes 1650, 1652 are provided through the cover 1604. Theholes 1650,1652 align with two hollow generally cylindrical bosses 1654which extend up from the floor 1601 of the housing 1602 to acceptretaining devices, such as screws, which secure the cover 1604 to thehousing 1602. In an alternative embodiment of the present invention,studs extend from the cover in alignment with the bosses 1654. Each studfits tightly within the opening in one of the bosses 1654 in order tosecure the cover 1604 to the floor 1601 of housing 1602.

In accordance with one embodiment of the present invention, thecartridge of the present invention is assembled by coupling the inputaspiration port assembly or inlet 1608 to a first port 1202 of thesensor assembly 400. The fluid coupling 1624 is coupled to the otherport 1204 of the sensor assembly 400. The combination of inputaspiration port assembly 1608, sensor assembly 400, and pump tubeassembly 1606 are then lowered into the housing 1602 and the protrusion1628 is inserted into the opening 1634. The pump tube 1636 is insertedinto openings 1638 in the wall 1609 of the housing 1602. A latch member300 is also provided and mounted in the housing as in the FIG. 3embodiment. The cover 1604 is then placed over, and secured to, thehousing 1602.

Once the cartridge 1600 is assembled, it may be installed in a bloodanalyzer, such as the blood analyzer 1700 illustrated in FIG. 17. Theblood analyzer of the present invention has a fluid connector (notshown, but like connectors 202 and 204 of FIG. 2a and 2 b) forconnection to port 1626 on the cartridge. The direct input aspirationport assembly 1608 provides a fluid flow path via inlet 1202 intocartridge sensor housing 400. The fluid flow path continues through thecartridge sensor housing via outlet 1404, through the pump tube assembly1606, through the right angle end fluid coupling 1626 and via the malefluid connector which mates with the fluid coupling 1626 to complete afluid flow path into the analyzer.

Fluids are pumped along the fluid flow path by a peristaltic roller pumpwhich includes a roller 1702 that massages the pump tube 1636. That is,the pump tube 1636 is preferably resilient enough to be stretched overthe roller 1636. The roller 1702 applies areas of alternating greaterand lesser pressure to the pump tube 1636, causing those portions of thepump tube 1636 that lie over an area of greater pressure to beinternally constricted and those areas of the pump tube 1636 that lieover an area of lesser pressure to be relaxed to essentially the fullunstressed diameter of the channel through the interior of the pump tube1636. As the roller 1702 rotates, the areas of alternating greater andlesser pressure traverse the pump tube to generate a peristaltic actionin the pump tube 1636.

It can be seen from the above description of the disposable cartridgethat the present invention provides a cartridge that: (1) is very easyto install, and thus may be installed with virtually no training; (2)establishes both electrical and fluid connections in one installationprocess with little or no risk of misaligning the electrical or fluidconnections of the cartridge with the corresponding connections of theblood analyzer; (3) includes an integral inexpensive and reliable pumptube assembly; (4) allows the user of the blood analyzer to see themovement of an analyte, gas bubbles, or reagent during analysis; (5) isinexpensive and thus may be disposed of without concern for excessivecost; (6) facilitates rapid, reliable replacement of the sensors of theblood analyzer; (7) reduces contact between blood elements and theanalyzer; (8) is compact in size; (9) can be used for sensors withdifferent analyte panels; and (10) allows one type of analyzer to acceptmany different types of sensors.

It should be understood that the cartridge of the present invention maybe provided in numerous alternative configurations. For example, aplurality of sensor assemblies may be coupled in series to provideredundancy or to increase the number or type of sensors that areprovided within the cartridge. Furthermore, straight fluid couplings mayreplace the right angle fluid couplings, and flexible tubing may be usedto alter the direction of the flow path. Furthermore, the pump tubingmay be directly coupled to the sensor assembly without the need for afluid coupling between the pump tubing and the sensor assembly.Furthermore, a wide variety of latching mechanisms may be used tosecurely latch the cartridge to a blood analyzer.

SUMMARY

A number of embodiments of the present invention have been described.Nevertheless, it will be understood that various modifications may bemade without departing from the spirit and scope of the invention. Forexample, while the present invention is described generally as beingfabricated using a thick film technique, any other well known layeredcircuit technique may be used, such as thin film, plating pressurizedlaminating, and photolithographic etching. Furthermore, substrates for anumber of sensor assemblies may be fabricated concurrently on a singlesection of ceramic material which has preferably been scored to allowfor easy separation into individual substrates after deposition of allof the components of the sensor assembly, and prior to installation inan encasement. Accordingly, it is to be understood that the invention isnot to be limited by the specific illustrated embodiment, but only bythe scope of the appended claims

What is claimed is:
 1. A blood analyzer sensor cartridge comprising: ahousing having means defining a chamber and a sensor assembly within thechamber; an elongated tubular member pivotally mounted to said housingdefining a first fluid port adapted for insertion in a sample containerfor direct introduction of a sample into said chamber; first fluid pathmeans in said housing communicating said first fluid port with saidsensor assembly; a second fluid port in said housing adapted forconnection to an analyzer; and second fluid path means in said housingcommunicating said sensor assembly with said second fluid port.
 2. Thecartridge of claim 1, wherein the mechanical mating of the cartridge toan analyzer is accomplished by movement of the cartridge in a straightline toward the analyzer.
 3. The cartridge of claim 1, wherein thehousing has an opening and the sensor assembly includes an electricalconnector which protrudes through the opening in the housing.
 4. Thecartridge of claim 3, wherein the sensor assembly includes a flow pathand a pump tube assembly, the pump tube assembly includes: (1) a flowpath therethrough; (2) a first end coupling for placing the flow paththrough the pump tube assembly in fluid communication with the sensorassembly flow path; and (3) a pump tube for mechanically interfacingwith a pump in order to create a peristaltic pumping action within thepump tube.
 5. The cartridge of claim 4, wherein said tubular member isan aspiration tube that is rigid and is connected by an elastomeric tubecoupling to said sensor assembly.
 6. A blood analyzer sensor cartridgecomprising: a housing having means defining a chamber and a sensorassembly within the chamber; a member defining a first fluid portadapted for insertion in a sample container for direct introduction of asample into said chamber; first fluid path means in said housingcommunicating said first fluid port with said sensor assembly; a secondfluid port in said housing adapted for connection to an analyzer; andsecond fluid path means in said housing communicating said sensorassembly with said second fluid port, wherein said member defining saidfirst fluid port comprises an elongated aspiration tube pivotallymounted to said housing for selective orientation within a range of upto ninety degrees.
 7. The cartridge of claim 6, wherein said aspirationtube is moveable from a protective recess in said housing to a positionnormal to a face of said housing.
 8. The cartridge of claim 7, whereinsaid aspiration tube comprises a lever for moving said aspiration tubeto and from said recess.
 9. The cartridge of claim 8, wherein saidsecond fluid path means comprises a pump tube assembly.
 10. Thecartridge of claim 9, wherein the pump tube assembly includes anelastomeric tube which mechanically interfaces with a pump roller inorder to create a peristaltic pumping action within the pump tube, thesensor assembly includes a flow path; and the pump tube assemblyincludes: (1) a flow path through the pump tube; and (2) a first endcoupled to said sensor assembly and a second end coupled to said secondfluid port for placing the flow path through the pump tube assembly influid communication with the flow path through the sensor assembly. 11.The cartridge of claim 10, wherein the pump tube assembly furthercomprising an end coupling, the end coupling being coupled between thesecond end of the pump tube assembly and the second housing fluid portat a right angle with respect to the longitudinal axis of the pump tube.12. The cartridge of claim 7, further comprising: an electricalconnector having electrical contacts; and an end coupling, the endcoupling being coupled between an end of the pump tube assembly and thesecond housing fluid port; wherein the end coupling protrudes beyond thehousing at least as far as the electrical contacts of the connector toguide the electrical contacts into proper alignment with mating contactsof the analyzer as the cartridge is installed on the analyzer.
 13. Thecartridge of claim 6, wherein said aspiration tube is moveable from agenerally vertical downward position to a generally horizontal position.14. The cartridge of claim 13, further comprising a lever for movingsaid aspiration tube between said downward position and said horizontalposition.
 15. The cartridge of claim 14, wherein said lever includes atab for activating a sensor.
 16. The cartridge of claim 14, wherein saidlever extends and retracts through an opening in said housing.
 17. Thecartridge of claim 6, wherein the sensor assembly has a cover and thecover has an opening through which analyte may be viewed in the sensorassembly during analysis.
 18. A blood analyzer sensor cartridgecomprising: a housing having chamber and a sensor assembly within thechamber; an elongated tubular member pivotly mounted to said housing anddefining a first fluid port adapted for insertion into a samplecontainer for direct introduction of a sample into said housing; a firstfluid path in said housing communicating said first fluid port with saidsensor assembly; a second fluid port in said housing adapted forconnection to an analyzer; and a pump tube defining a second fluid pathcommunicating said sensor assembly with said second fluid port.
 19. Thecartridge of claim 18, wherein said tubular member defining said firstfluid port comprises an elongated aspiration tube pivotally mounted tosaid housing for selective orientation within a range of up to ninetydegrees between a substantially vertical orientation and a substantiallyhorizontal orientation.
 20. The cartridge of claim 19, wherein saidaspiration tube is moveable from a protective recess in said housing toa position normal to a face of said housing.